PUBLICATION
A systematical comparison of anti-angiogenesis and anti-cancer efficacy of ramucirumab, apatinib, regorafenib and cabozantinib in zebrafish model
- Authors
- Wu, J.Q., Fan, R.Y., Zhang, S.R., Li, C.Y., Shen, L.Z., Wei, P., He, Z.H., He, M.F.
- ID
- ZDB-PUB-200210-1
- Date
- 2020
- Source
- Life sciences 247: 117402 (Journal)
- Registered Authors
- Keywords
- Apatinib, Cabozantinib, Gastric cancer, Ramucirumab, Regorafenib, Zebrafish xenograft tumor model
- MeSH Terms
-
- Angiogenesis Inhibitors/pharmacology*
- Anilides/pharmacology*
- Animals
- Animals, Genetically Modified
- Antibodies, Monoclonal, Humanized/pharmacology*
- Antineoplastic Agents/pharmacology*
- Disease Models, Animal
- Female
- Male
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Physiologic/drug effects
- Phenylurea Compounds/pharmacology*
- Pyridines/pharmacology*
- Stomach Neoplasms/blood supply
- Stomach Neoplasms/drug therapy
- Zebrafish/embryology
- PubMed
- 32035930 Full text @ Life Sci.
Citation
Wu, J.Q., Fan, R.Y., Zhang, S.R., Li, C.Y., Shen, L.Z., Wei, P., He, Z.H., He, M.F. (2020) A systematical comparison of anti-angiogenesis and anti-cancer efficacy of ramucirumab, apatinib, regorafenib and cabozantinib in zebrafish model. Life sciences. 247:117402.
Abstract
Aims Gastric cancer (GC) is one of the most common malignant tumors in the world. Anti-angiogenic therapy is a useful strategy for the treatment of advanced GC. This study was aimed to systemically compare the anti-angiogenesis, anti-cancer efficacy, as well as the safety of four known anti-angiogenic drugs, namely ramucirumab, apatinib, regorafenib and cabozantinib.
Main methods Anti-angiogenic effect was evaluated for the intersegmental vessels (ISVs) and subintestinal veins (SIVs) formation in the Tg (fli-1: EGFP) zebrafish embryos. Anti-cancer efficacy was tested for the in vivo cell proliferation in cell line derived tumor xenograft (CDX) model based on Tg (fli-1: EGFP) zebrafish embryos.
Key findings All four drugs exhibited anti-angiogenic abilities and tumor inhibition effects in fli-1: EGFP transgenic zebrafish. Using zebrafish xenografted model, we found that effectiveness of ramucirumab in anti-GC-proliferation is better than apatinib, regorafenib and cabozantinib. The combination of anti-angiogenic drugs and cisplatin showed no significant benefit in tumors. Meanwhile, toxicity assay showed that all tested anti-angiogenic drugs could cause cardiovascular-related side effects. The therapeutic index (LD50/ED50) of cabozantinib is higher than apatinib and regorafenib, suggesting a potential as an anti-GC drug.
Significance The comparison of GC-related anti-angiogenic drugs was first reported. It was found that cabozantinib had a potential as an anti-GC drug. Zebrafish model was an ideal animal model for the research of anti-angiogenic behaviors.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping